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Variegate porphyria

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Variegate porphyria
Other namesMixed hepatic porphyria,[1]Mixed porphyria,[1]South African genetic porphyria,[1]: 525 and South African porphyria.[2]
Protoporphyrinogen IX
SpecialtyEndocrinologyEdit this on Wikidata
Symptomsskin problems, Enzymedifficiency.
Causesgenetic mutations.
Treatmentliver transplants.

Variegate porphyria,also known byseveral other names,is anautosomal dominantporphyria[3]that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect theskin.The disorder results from low levels of theenzymeresponsible for the seventh step inhemeproduction. Heme is a vital molecule for all of the body'sorgans.It is a component ofhemoglobin,the molecule that carriesoxygenin theblood.

Signs and symptoms[edit]

When symptoms occur, they can include acute attacks (similar toacute intermittent porphyria) or skin damage. Acute attacks usually begin in adulthood and cause abdominal pain,vomiting,diarrhoeaandconstipation.During an attack, a person may also experience muscle weakness,seizures,and mental changes such as anxiety andhallucinations.These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certainhormonesand stress.[citation needed]

Some people with variegate porphyria have skin that is overly sensitive tosunlight(photosensitive). Areas of skin exposed to the sun develop severe blistering, scarring, changes inpigmentation,and increased hair growth. Exposed skin becomes fragile and is easily damaged.[citation needed]

Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life.[citation needed]

Genetics[edit]

Variegate porphyria has an autosomal dominant pattern of inheritance.

Mutationsin thePPOXgenecause variegate porphyria.[4]The PPOX gene makes a membrane boundmitochondrialenzyme calledprotoporphyrinogen oxidase,which is critical to the chemical process that leads to heme production. The activity of this enzyme is reduced by 50 percent in most people with variegate porphyria. In severe cases that begin early in life, the enzyme is almost completely inactive. Nongenetic factors such as certain drugs, stress, and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity ofprotoporphyrinogen oxidasedisrupts heme production and allows byproducts of the process to accumulate in the liver, triggering an acute attack.[citation needed]

Variegate porphyria is inherited in anautosomal dominantpattern, which means the defective gene is located on anautosome,and inheriting one copy of the defective gene from an affected parent is sufficient to cause the disorder. More severe cases result from inheriting two copies of the defective gene.[citation needed]

The entire PPOX gene has about 8kb with 13 exon sequences. It was successfully cloned from a cDNA library in 1995 revealing that, after processing, it is 477nucleotideslong. It has previously been thought that the PPOX gene was located on humanchromosome 14,[5]however mapping experiments (FISH) have shown that it is near 1q23.[6]An additional aggravating mutation affecting variegate porphyria can be found at 6p21.3 on theHFEgene.[7]

A 2006 clinical, biochemical and mutational study of eight Swiss variegate porphyria patients and their families found four novel PPOX gene mutations believed to be unique to the Swiss population.[8]

Diagnosis[edit]

Diagnosis is by finding raised urine porphyrins, raised faecal porphyrins, markedly raised plasma porphyrins (pathognomic) and finding photosensitive cutaneous lesions on clinical examination.[citation needed]

Treatment[edit]

Liver transplanthas been used in the treatment of this condition.[9]

Epidemiology[edit]

InSouth Africa,the prevalence of variegate porphyria is approximately 1 in 300.[10]In Finland, the prevalence is approximately 1 in 75,000.[11]

It is also found inArgentina,[12]Sweden,[13]andAustralia.[14]

References[edit]

  1. ^abcJames, William D, Berger, Timothy G, et al. (2006).Andrews' Diseases of the Skin: clinical Dermatology.Saunders Elsevier.ISBN978-0-7216-2921-6.
  2. ^Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007).Dermatology: 2-Volume Set.St. Louis: Mosby.ISBN978-1-4160-2999-1.
  3. ^"porphyria variegata"atDorland's Medical Dictionary
  4. ^Frank J, Christiano AM (1998)."Variegate porphyria: past, present and future".Skin Pharmacol. Appl. Skin Physiol.11(6): 310–20.doi:10.1159/000029854.PMID10343202.S2CID40665725.
  5. ^Bissbort S, Hitzeroth HW, du Wentzel DP, et al. (July 1988). "Linkage between the variegate porphyria (VP) and the alpha-1-antitrypsin (PI) genes on human chromosome 14".Hum. Genet.79(3): 289–90.doi:10.1007/BF00366255.PMID3261272.S2CID27271722.
  6. ^Roberts AG, Whatley SD, Daniels J, et al. (December 1995)."Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23".Hum. Mol. Genet.4(12): 2387–90.doi:10.1093/hmg/4.12.2387.PMID8634714.
  7. ^de Villiers JN, Hillermann R, Loubser L, Kotze MJ (August 1999)."Spectrum of mutations in the HFE gene implicated in haemochromatosis and porphyria".Hum. Mol. Genet.8(8): 1517–22.doi:10.1093/hmg/8.8.1517.PMID10401000.
  8. ^Schneider-Yin X, Minder EI (August 2006)."Swiss patients with variegate porphyria have unique mutations".Swiss Med Wkly.136(31–32): 515–9.doi:10.4414/smw.2006.11472.PMID16947091.S2CID33670384.
  9. ^Stojeba N, Meyer C, Jeanpierre C, et al. (July 2004)."Recovery from a variegate porphyria by a liver transplantation".Liver Transpl.10(7): 935–8.doi:10.1002/lt.20136.PMID15237381.
  10. ^Arceci, Robert.; Hann, Ian M.; Smith, Owen P. (2006).Pediatric hematolog.Malden, Mass.: Blackwell Pub.ISBN978-1-4051-3400-2.
  11. ^Mustajoki, P. (1980). "Variegate porphyria. Twelve years' experience in Finland".The Quarterly Journal of Medicine.49(194): 191–203.PMID7433635.
  12. ^Rossetti MV, Granata BX, Giudice J, Parera VE, Batlle A (2008)."Genetic and biochemical studies in Argentinean patients with variegate porphyria".BMC Med. Genet.9:54.doi:10.1186/1471-2350-9-54.PMC2467414.PMID18570668.
  13. ^Wiman A, Harper P, Floderus Y (August 2003). "Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria".Clin. Genet.64(2): 122–30.doi:10.1034/j.1399-0004.2003.00116.x.PMID12859407.S2CID38314848.
  14. ^Rossi E, Chin CY, Beilby JP, Waso HF, Warnich L (September 2002). "Variegate porphyria in Western Australian Aboriginal patients".Internal Medicine Journal.32(9–10): 445–450.doi:10.1046/j.1445-5994.2002.00274.x.PMID12380696.S2CID34572600.{{cite journal}}:CS1 maint: multiple names: authors list (link)

This article incorporates public domain text fromThe U.S. National Library of Medicine

External links[edit]

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